Our objective is to determine the conditions necessary for immunologic activation of leukemia viruses. The immunologic events occurring in certain kinds of immune responses and the mechanism of these responses in initiating C-type virus activation will be studied. Attempts will be made to activate C-type viruses from lymphocytes of cattle with "preleukemic" lymphocytosis. An in depth study of factors involved in in vitro activation of C-type viruses will be undertaken. We will direct all efforts to detection of virus activation resulting from (1) immunologic events involved in "allogeneic cell interactions", such as mixed lymphocyte cultures (MLC), (2) soluble factors released by cells undergoing allogeneic interaction (MLC), (3) immune response to a specfic antigen in vitro, (4) soluble factors released by cells in vitro when undergoing an immune response to a specific antigen, (5) mitogen treatment of lymphocytes, (6) soluble factors released by cells undergoing blastogenesis in response to mitogen stimulation, and (8) addition of subcellular material from lymphocytes from cows with lymphoma. An attempt will be made to determine cell types associated with virus production. Immunoperoxidase techniques will be employed using the electron microscope and cells associated with C-type virus production will be identified. Cultures of bovine lymphocytes will be prepared from animals which have been inoculated with concentrated suspensions of C-type viruses, but which are not yet showing signs of lymphocytosis or leukemia. These cells will be cultured in an attempt to activate latent C-type viruses if indeed such a virus is present in these animals. In all of the above studies, substances which will activate virus production will be analyzed by physical and biochemical procedures to concentrate and purify the factor(s) which may be important in the virus activation process.